Table 1.

Summary findings: 12 cases involving behavior and mood changes in association with cholesterol-lowering drug use

Case	Agea	Sex	Drug	Dose (mg/day)	Behavioral and mood effect	Causality assignmentb	Factors supporting causal association
1	40s	Male	Simvastatin	80	Irritability, detachment, joylessness, anxiety, impatience, reduced social activities, depressive mood, adjustment disorder, completed suicide	Possible	R O: fatigue, insomnia, cognitive/attention problems, temperature dysregulation, skin irritation RF: high body mass index, high-dose statin Comment: tight temporal association to statin onset also supports a causal connection (completed suicide precluded an attempt at statin discontinuation)
2	50s	Female	Simvastatin	10	Depression, joylessness, loss of appetite	Probable	R, D O: muscle weakness, muscle cramps, muscle pain, shortness of breath, fatigue/lack of energy RF: thyroid disorder, female gender
3	50s	Male	Atorvastatin	20, 10	Depression, joylessness, hopelessness, aggression, irritability	Probable	R, D O: weight gain
4	40s	Male	Atorvastatin	10	Depression, aggression, impatience, irritability, paranoia, completed suicide	Possible	R: possible O: memory problems, sleep problems, hearing loss, muscle pain, skin irritation
5	30s	Male	Fenofibrate + rosuvastatin, atorvastatin	Unknown	Aggression, irritability, divorce	Probable	R, D O: memory problems, fatigue RF: thyroid problems, high triglycerides, fenofibrate combination
6	40s	Male	Lovastatin	Unknown	Depression, mania, suicide attempts, dyscontrol of bipolar episodes	Possible	R FH (psychiatric)
7	Teens	Male	Atorvastatin	20	Depression, nightmares, anxiety, attention/concentration problems, completed suicide	Definite	R, D, RC FH (psychiatric)
8	60s	Male	Simvastatin	10	Depression, hopelessness, aggression, irritability, loss of interest in activities and socializing, completed suicide	Possible	R O: muscle and joint pain FH (psychiatric)
9	60s	Male	Simvastatin Atorvastatin	20 10	Irritability, aggression, increased emotional response	Definite	R, D, RC O: memory problems, cognitive problems, skin irritation, muscle pain
10	30s	Male	Atorvastatin	10–20 40	Violent ideation, anxiety	Probable	R, D FH RF
11	50s	Male	Atorvastatin Simvastatin	20 20	Aggression, irritability	Definite	R, D, RC O: fatigue RF: hypertension
12	40s	Male	Lovastatin, rosuvastatin, atorvastatin, simvastatin, pravastatinc	Varying doses (40 mg-1 mg)	Aggression, irritability, violent ideation	Definite	R, D, RC O: cognitive problems, shortness of breath, muscle pain

D dechallenge evidence (discontinued the agent and experienced improvement), FH family history of adverse effects from cholesterol drugs, O development of other recognized adverse events of cholesterol drugs (for review of data connecting statins to these other adverse events, see Tables 1, 7, and 8 of Golomb and Evans [39]), R development of marked personality change sustained while on drug, RC rechallenge evidence (reinitiated the agent and experienced recurrence), RF other known risk factors for statin adverse events (for review of data connecting risk factors to statin adverse events, see Table 4 of Golomb and Evans [39])

^aAge listed in decades for de-identification purposes due to the sensitive nature of cases

^bAdverse drug reaction causality assignment was generated using the Naranjo criteria [38]

^cPatient tried pravastatin but did not experience a behavioral effect